The principal goals of the proposal are two-fold: (1) to determine the effects of alcohol on hepatic collagen metabolism and (2) to investigate hormonal influences which may regulate the activity of liver alcohol dehydrogenase and their physiological significance. The effect of ethanol feeding will be determined in rats on hepatic pathways of metabolism in the synthesis and degradation of proline, on collagen synthesis, measured in vitro with tissue slices and in vivo by the incorporation of labeled proline into hepatic collagen, and on the localization of basement membranes, Type I and Type III collagen using immunohistochemical methods. In monkeys, yearly determinations of the effect of ethanol feeding on liver collagen proline hydroxylase activity, collagen deposition, activity of lysosomal enzymes, and histochemistry of acid phosphatase by light and electron microscopy will be continued. The influence of growth hormone administration and of hypophysectomy, previously demonstrated to change the activity of hepatic alcohol dehydrogenase in male rats, will be investigated on the enzyme activity in female rats. Also studied will be the effects of castration, the administration of testosterone to castrated and hypophysectomized animals, of growth hormone to castrated animals, and the possible interactions between growth hormone and testosterone in regulating liver alcohol dehydrogenase. The kinetic and electrophoretic characteristics of the increased enzyme will be determined. The enzyme will be purified and a radioimmunoassay will be developed to determine whether increases in the enzyme activity are the result of activation of a precursor or an increase in enzyme protein, and if the latter, whether this is due to increased synthesis, decreased degradation or a combination of both processes. Possible changes in affinity of the increased enzyme activity for physiological substrates such as vitamin A and farnesol will be investigated. Rates of ethanol metabolism will be determined in situations in which there is increased alcohol dehydrogenase activity.